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Proteolysis of CCN1 by plasmin: functional implications
Usha R Pendurthi1, Tien T Tran, Marina Post
1Biomedical Research Division, The University of Texas Health Center at Tyler, Tyler, Texas 75708, USA. usha.pendurthi@uthct.edu
Cancer Research
|November 4, 2005
Summary
Plasmin cleaves the matricellular protein CCN1 (Cysteine-rich 61) from the extracellular matrix. This released CCN1 then promotes endothelial cell migration, suggesting a role in diseases like cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Plasmin degrades extracellular matrix (ECM) and mobilizes sequestered growth factors, impacting pathophysiologic processes.
- Cysteine-rich 61 (CCN1) is a matricellular protein upregulated in cancer and vascular diseases.
Purpose of the Study:
- To investigate if plasmin liberates CCN1 from the ECM.
- To determine if released CCN1 modulates endothelial cell migration.
Main Methods:
- Treatment of breast carcinoma cells (MDA-MB-231) with plasmin.
- Analysis of released CCN1 in conditioned medium.
- Experiments using recombinant CCN1 and CCN1-specific antibodies.
- Assessment of endothelial cell migration.
Main Results:
- Plasmin treatment released a truncated form of CCN1 (28 kDa) from carcinoma cells.
- Plasmin effectively cleaved recombinant CCN1, while thrombin and other proteases did not.
- Conditioned medium from plasmin-treated cells enhanced endothelial cell migration, an effect blocked by CCN1 antibodies.
Conclusions:
- Plasmin liberates the signaling protein CCN1 from the ECM.
- Proteolysis of CCN1 by plasmin may contribute to pathophysiologic processes, including tumor angiogenesis.